Proton scattering analysis system

ABSTRACT

Disclosed are systems and methods for characterizing interactions or proton beams in tissues. In certain embodiments, charged particles emitted during passage of protons, such as those used for therapeutic and/or imaging purposes, can be detected at relatively large angles. In situations where beam intensity is relatively low, such as in certain imaging applications, characterization of the proton beam with charged particles can provide sufficient statistics for meaningful results while avoiding the beam itself. In situations where beam intensity is relatively high, such as in certain therapeutic applications, characterization of the proton beam with scattered primary protons and secondary protons can provide information such as differences in densities encountered by the beam as it traverses the tissue and dose deposited along the beam path. In certain situations, such beam characterizations can facilitate more accurate planning and monitoring of proton-based therapy.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

Any and all applications for which a foreign or domestic priority claimis identified in the Application Data Sheet as filed with the presentapplication are incorporated by reference under 37 CFR 1.57 and made apart of this specification.

BACKGROUND

1. Field

The invention relates to the field of radiation therapy and to systemsand methods for analyzing interactions of protons with tissue or othermaterials for imaging and to improve diagnosis and accuracy of therapydelivery.

2. Description of the Related Art

Proton beam therapy has known and potential benefits in treatment of awide variety of disease conditions. Protons at certain energies exhibita useful characteristic of a relatively high degree of controllabilityand selective transfer of energy to target tissue with relatively lowundesired transfer of energy to non-target tissue. Protons exhibit thephysical characteristic of a Bragg peak where a substantial fraction ofthe energy of a beam of accelerated protons is delivered within arelatively narrow penetration depth and where the depth can be selectedand controlled based on the characteristics of material through whichthe proton beam passes and the energy of the protons. The highest energydeposition per unit length (LET) is typically exhibited at the end ofrange of such a proton beam, e.g. at the Bragg peak, and this alsocorresponds to the region of maximum absorbed dose. The characteristicsof protons result in a relatively low entrance dose to non-target tissueupstream of the target region and a relatively low (approachingnegligible) exit dose (e.g. to non-target tissue downstream from thetarget region with proper selection of beam energies).

This feature allows a clinician to adjust the proton energy such thatthe depth of the Bragg peak coincides with the spatial location oftarget tissue. In many applications, a collimator is used to control thefocus of the proton beam. A focused proton beam can be raster scannedand/or modulated to deliver a selected radiation dose to a distributedtarget region with significantly reduced undesired transfer of energy tonon-target tissues, for example as occurs with photonic radiationtherapy.

It will be understood however that calculation of an appropriate protondose and selection of beam energy to achieve a desired depth or range isdependent on accurate knowledge of the characteristics of the materialsthrough which the beam will pass. In some implementations, x-ray imagingand/or computed tomography (CT) is utilized to obtain indications of theinternal structures and compositions of the patient, including theintended target region of the proton therapy and intervening non-targettissue. However, inaccuracies and/or uncertainties can arise in imagesthat are based on electron density distributions, thereby leading tocorresponding uncertainties in dose and proton range values.

SUMMARY

In certain embodiments, the present disclosure relates to a protontherapy system having a support device configured to support a volume oftissue and expose at least a portion of the volume of tissue to a beamof protons. The beam of protons is configured for therapeutic treatmentof at least a portion of the volume of tissue, with the beam of protonsdefining a beam axis extending through the volume of tissue. The systemfurther includes a charged particle detector disposed relative to thevolume of tissue and configured so as to detect charged particlesresulting from interactions of the beam of protons with the volume oftissue. The charged particle detector has an acceptance range about adetector axis that extends through a selected location in the volume oftissue and along the beam axis, and the detector axis forms an anglewith respect to a forward direction of the beam axis. The angle iswithin a range of approximately 20 degrees to 90 degrees. The chargedparticle detector is configured to facilitate reconstruction of tracksassociated with the detected charged particles, and the detectionresults in generation of signals. The system further includes acomputing device in communication with the detector and configured toreceive the signals and generate data having information that allows thereconstruction of the tracks so as to allow estimation of locations ofthe interactions in the volume of tissue.

In certain embodiments, the present disclosure relates to a method forplanning a proton therapy. The method includes positioning a patient ona support device so as to allow exposure of a portion of the patient toa beam of protons that is configured for therapeutic treatment andtravelling generally along a beam path within the patient. The methodfurther includes delivering one or more spills of protons to thepatient, with each spill having an intensity associated with thetherapeutic beam of protons. The method further includes determining aprofile of the beam path based on interaction of the spill of protons inthe patient. The profile includes scattering locations of primaryprotons associated with the spill of protons and vertex locations ofsecondary protons emitted from within the patient. The profile providesinformation about differences in densities along the beam path. Theprimary and secondary protons are detected and characterized at an anglerelative to the beam path, with the angle being within a range ofapproximately 20 degrees to 90 degrees. The method further includesadjusting the beam configuration based on the detected profile.

In certain embodiments, the present disclosure relates to a method formonitoring a proton therapy. The method includes positioning a patienton a support device so as to allow exposure of a portion of the patientto a beam of protons that is configured for therapeutic treatment andtravelling generally along a beam path within the patient. The methodfurther includes delivering one or more spills of protons to thepatient. The method further includes detecting interactions of the spillof protons in the patient. The detected interactions include scatteringlocations of protons from within the patient. The detected interactionsprovide information about numbers of scattering protons at thelocations. The protons are detected at an angle relative to the beampath, with the angle being within a range of approximately 20 degrees to90 degrees. The method further includes estimating a dose deposited forthe spill of protons based on the numbers of scattering protons at thelocations.

In certain embodiments, the present disclosure relates to a proton basedimaging and therapy system. The system includes a support deviceconfigured to support a patient and expose at least a portion of thepatient to a beam of protons that is configurable for a therapy mode andan imaging mode, with the beam of protons defining a beam axis extendingthrough the patient. The system further includes a charged particledetector mounted to a mounting mechanism so as to allow positioning ofthe detector at first and second positions relative to the beam axis.The first position is downstream of the patient along the beam axis, andthe second position is at an angle θ with respect to the beam axis.

The angle θ is within a range of approximately 20 to 90 degrees. Thedetector is configured so as to detect charged particles resulting frominteractions of the beam of protons with the patient. The system furtherincludes a control system configured to position the detector at thefirst position and deliver the beam of protons in the imaging mode whenthe proton based imaging and therapy system is being operated forimaging purpose, and to position the detector at the second position anddeliver the beam of protons in the therapy mode when the proton basedimaging and therapy system is being operated for therapy purpose.

Certain embodiments of the present disclosure provide improved abilityto monitor and analyze interaction between an incident proton beam andtarget tissue as well as a spatial location of a proton beam.Embodiments include a system for determining positions in space,including through patient tissue, through which accelerated protons passand to utilize this information to mathematically reconstruct an initialor nominal path from which protons can become deflected. The system canalso be capable in addition or as an alternative to measure an impactenergy and thereby determine an energy loss of an incident proton.Embodiments can determine indications of the elemental or atomic numberconstitution of material that the proton has impacted. Embodimentsprovide to the clinician a measured confirmation of an actual path of aproton beam independent of any other aiming or predictive measures.

One embodiment includes, a proton therapy system for delivery of atherapeutic proton beam comprising a plurality of protons towards atarget region of a patient, the proton therapy system comprising apatient support configured for supporting a patient, a proton source forgenerating a therapeutic proton beam, a proton delivery deviceconfigured to receive the therapeutic proton beam from the proton sourceand direct the therapeutic proton beam at a mean initial energy along aninitial path towards a target region of the patient supported on thepatient support, wherein respective paths of at least some of theprotons of the therapeutic proton beam are deflected in response tocontact with the patient, at least one sensor arranged proximal thetarget region and configured to measure at least one of an impactlocation of incident protons and an impact energy of incident protons,and a processor in communication with the at least one sensor andconfigured to calculate at least one of an amount of deflection of theincident protons from the initial path and an incident energy loss fromthe initial proton energy and to provide an indication of at least oneof an electron density within the target region through which theprotons pass and an atomic number corresponding to the target region.

In certain embodiments, a method of analyzing accelerated protons in aproton therapy system comprises generating a beam of acceleratedprotons, directing the proton beam at a target region, arranging one ormore sensors adjacent the target region, monitoring at least one ofenergy and a spatial location of protons incident on the one or moresensors, and calculating one or more of an indication of electrondensity within the target region and atomic number of the target region.These and other objects and advantages of the invention will become moreapparent from the following description taken in conjunction with theaccompanying drawings.

Nothing in the foregoing summary or the following detailed descriptionis intended to imply that any particular feature, characteristic, orcomponent of the disclosed devices is essential.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features will now be described with reference to thedrawing summarized below. These drawings and the associated descriptionare provided to illustrate specific embodiments, and not to limit thescope of the scope of protection.

FIG. 1 schematically depicts a proton beam incident on a target volumehaving materials such as tissue.

FIG. 2 schematically depicts an example interaction system having aproton interacting with a target nucleus, where the interaction systemcan arise from the proton beam and target volume configuration of FIG.1.

FIG. 3 shows examples of products that can be yielded by the interactionsystem of FIG. 2.

FIG. 4 schematically depicts an example setup configured to detectcertain charged particles resulting from interactions of differentenergy proton beams with a head shaped phantom.

FIG. 5A shows a graphic depiction of proton tracks resulting fromcomputer simulation of interactions of 1,000 protons with kinetic energyof approximately 100 MeV with an approximation of the example setup ofFIG. 4.

FIG. 5B shows a graphic depiction of substantially all secondaryparticle tracks (including photons) resulting from the same exampleconfiguration of FIG. 5A.

FIG. 6A shows a graphic depiction of proton tracks resulting fromcomputer simulation of interactions of 1,000 protons with kinetic energyof approximately 250 MeV with an approximation of the example setup ofFIG. 4.

FIG. 6B shows a graphic depiction of substantially all secondaryparticle tracks (including photons) resulting from the same exampleconfiguration of FIG. 6A.

FIG. 7A shows a 100 MeV therapeutic pencil proton beam profile as itpasses through the head phantom, where the beam profile is generatedbased on reconstruction of detected charged particles resulting from theexample setup of FIG. 4.

FIG. 7B shows a beam profile of the beam of FIG. 7A at 8 cm depth.

FIG. 7C shows a beam profile of the beam of FIG. 7A at entrance.

FIG. 8A shows a 250 MeV therapeutic pencil proton beam profile as itpasses through the head phantom, where the beam profile is generatedbased on reconstruction of detected charged particles resulting from theexample setup of FIG. 4.

FIG. 8B shows a beam profile of the beam of FIG. 8A at 10 cm in aphantom.

FIG. 8C shows a beam profile of the beam of FIG. 8A at entrance.

FIG. 9A shows a similar 250 MeV proton beam profile as that of FIG. 8,but where the incident beam is collimated to have a width of about 3.5mm.

FIG. 9B shows a beam profile of the beam of FIG. 9A.

FIG. 9C shows another beam profile of the beam of FIG. 9A.

FIG. 10 schematically depicts the example setup of FIG. 4, but withoutthe head phantom.

FIG. 11 shows a graphic depiction of secondary particle tracks(including photons) resulting from computer simulation of interactionsof 1,000 protons with kinetic energy of approximately 250 MeV with airin the example setup of FIG. 10.

FIG. 12A shows a 250 MeV therapeutic pencil proton beam profile as itpasses through the air, where the beam profile is generated based onreconstruction of detected charged particles resulting from the examplesetup of FIG. 10.

FIG. 12B shows a beam profile of the beam of FIG. 12A.

FIG. 13 shows that in certain embodiments, one or more detectors can bepositioned relative to the target volume to capture and detect certaintypes of proton-nucleus interactions.

FIG. 14 shows an example phantom object defined in a GEANT4 simulationalgorithm, where simulation of proton interaction with the phantom canbe utilized to estimate a likely angular distribution of protons and/orother charged particles for determining positioning of the one or moredetectors of FIG. 13.

FIG. 15 shows an example sensitive volume that can be defined in theGEANT4 algorithm to facilitate the estimation of the angulardistribution of FIG. 14.

FIG. 16 shows an angular distribution of scattered protons resultingfrom interaction of 100 MeV protons with the phantom in the simulationconfiguration of FIG. 15.

FIG. 17 shows an angular distribution of scattered protons resultingfrom interaction of 250 MeV protons with the phantom in the simulationconfiguration of FIG. 15.

FIG. 18 shows a scatter plot from data for an approximately 100 MeVproton beam profile as it passes through a phantom, where the beamprofile is generated based on reconstruction of detected protons withdetectors positioned based on the simulated angular distribution of FIG.16.

FIG. 19 shows a scatter plot from data for an approximately 250 MeVproton beam profile as it passes through a phantom, where the beamprofile is generated based on reconstruction of detected protons withdetectors positioned based on the simulated angular distribution of FIG.17.

FIGS. 20A and 20B illustrate example configurations of embodiments of aproton radiation therapy system where one or more features of thepresent disclosure can be implemented.

FIG. 21 illustrates a configuration that can be an example of thedetection configuration of FIG. 13.

FIG. 22 illustrates another configuration that can be an example of thedetection configuration of FIG. 13.

FIGS. 23A and 23B illustrate transverse views of charged particle trackswhose rigidity can be characterized by, for example, application ofmagnetic field.

FIG. 24 illustrates a side section view of an incident proton beam andembodiments of protons sensors and illustrating divergence of theincident proton beam.

FIG. 25 is a schematic illustration of an exemplary deflected incidentproton and various characteristics thereof as measured by embodiments ofa proton scattering analysis system.

FIG. 26 illustrates an embodiment of a sensor that can detect chargedparticles.

FIG. 27 is a flow chart of embodiments of methods of analyzing a protonbeam, for example in a proton therapy system, based on one or morefeatures of the present disclosure.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

Thepresent disclosure generally relates to utilizing detected productsof certain types of proton-nucleus collision interactions. As describedherein, such detected products can be utilized in proton-based therapyand/or imaging systems.

FIG. 1 schematically depicts a configuration 500 where a target volume504 is subjected to a beam of protons 502. The proton beam 502 can begenerated and delivered to the target volume 504 in a number ofdifferent configurations (e.g., average kinetic energy, average beamwidth, average number of protons per spill, etc.) by known devices andmethods; and thus, further description is not needed herein.

In certain situations, the target volume 504 can be a tissue beingcharacterized. Such a tissue can be part of a human patient. Althoughmany of the examples described herein are in the context of therapy forand/or imaging of human patients, it will be understood that the tissuecan also be part of a non-living animal, and the animal (living or not)can include humans as well as non-humans.

FIG. 2 depicts a collision interaction system 530 where a proton 510(e.g., part of the beam 502 of FIG. 1) collides with a nucleus 520 of anatom in the target volume 504. In certain situations where protons areused for therapy, it can be advantageous to characterize the targetvolume based on interactions of protons that are same or similar tothose of the therapeutic beam. As generally known, use of photon (e.g.,X-ray) based imaging techniques such as computed tomography (CT) rely ondifferences in absorption among, for example, soft tissue and skeletalfeatures. Accordingly, such techniques applied to proton treatmentplanning is limited by fundamental differences in physical interactionprocesses—between photons and protons—and therefore can be subject toinherent inaccuracy. For example, X-ray based images typically depictskeletal structures relatively well; but a tumor being treated is notimaged as well or at all.

In the proton-nucleus interaction 530 of FIG. 2, the nucleus 520 can beany one of the nuclei found in the target volume. For example, thenucleus 520 can be that of a commonly found element in tissue, such ascarbon, nitrogen and oxygen. Further, the proton's interactions with thenucleus 520 can have impact parameter values ranging from zero (centralcollision) to those associated with peripheral interactions. The type ofnucleus 520, the impact parameter, and energy of the incident proton 510are some of a number of factors that can influence the type and quantityof products generated from the proton-nucleus interaction of FIG. 2.

FIG. 3 shows that the interaction system 530 can yield interactionproducts 540 such as scattered protons, charged nucleus fragments,charged hadrons such as pions, charged leptons such as electrons andmuons, and photons such as gammas. In certain embodiments, one or moreconfigurations of the present disclosure can be configured to detectcharged particles in kinematic regions associated with probing of thenucleus by the proton beyond the Coulomb barrier.

For the purpose of description herein, the scattered protons can includeprotons from the incident beam (primary protons), as well as secondaryprotons resulting from interactions of the incident proton beam with thetarget volume. The charged nucleus fragments can include fragments fromtarget nuclei resulting from collisions with the incident protons. Thecharged hadrons can include pions and kaons; although such hadrons willrequire that the collision energy be sufficiently high to meet theirrespective production threshold energies. The charged leptons caninclude electrons and muons.

FIGS. 4-9 show examples of simulations and measurements where chargedparticles are utilized for characterizing interactions of protons with atarget volume. FIG. 4 shows an example configuration 550 where a protonbeam 552 is provided to a target volume 554 such as a head shapedphantom. A detector 556 downstream of the target volume 554 can beconfigured to provide functionalities such as triggering and the like inknown manners.

In the example configuration 550, a detector assembly 558 is positionedrelative to the target volume 554 so as to capture and detect chargedparticles emitted at or near about 90 degrees (in laboratory frame). Thedetection and tracking of charged particles can be achieved in a numberof known ways. For example, a number of strip detectors (such as Sistrip detector) can be arranged appropriately to allow determination oflocations of a charged particle at two or more planes, thereby allowingdetermination of the charged particle's path within the detectorassembly. Implementation of various strip detectors, readout of signals,and construction of tracks within the detector assembly can be achievedby known devices and methods.

FIGS. 5 and 6 show graphical representations of a computer simulation ofthe example configuration of FIG. 4. The computer simulation wasfacilitated by known GEANT4 simulation software that can be configuredand executed in manners known in the art; thus additional details arenot necessary for the purpose of description herein. As shown, the headshaped phantom of the measurement setup (550 in FIG. 4) is approximatedas an elliptical shaped object.

FIG. 5A graphically displays tracks representative of secondary protonsresulting from 1,000 interaction events of 100 MeV protons with thetarget volume. FIG. 5B graphically displays tracks representative ofsubstantially all secondary particles (including photons) resulting fromthe same events as that of FIG. 5A.

FIG. 6A graphically displays tracks representative of secondary protonsresulting from 1,000 interaction events of 250 MeV protons with thetarget volume. FIG. 6B graphically displays tracks representative ofsubstantially all secondary particles (including photons) resulting fromthe same events as that of FIG. 6A.

In FIGS. 5 and 6, the non-proton charged particles are essentiallyelectrons. In situations where the beam energy is higher, charged pionscan also be produced and detected.

It should be noted that in the simulation depicted in FIGS. 5 and 6,only 1,000 protons are provided for interactions; thus, relatively smallnumbers of protons are shown to be directed in the acceptance range ofthe detector. On the other hand, however, even the 1,000 events canprovide ample charged particles to the detector. Thus, as describedherein, detection of charged particles can provide flexibility inpositioning and/or configuring of one or more detectors.

For example, a detector can be configured to detect charged particleswithout a particle identification capability. Such a detector can berelatively simple, and the relatively high statistics associated withall charged particles can allow use of the detector in low beamintensity situations and/or positioning of the detector at angles (e.g.,large angles) where proton density is relatively low.

In another example, a detector can be configured to facilitate particleidentification. Specific particles such as protons can be distinguishedfrom other charged particles so as to allow use of protons as targetvolume characterizing probes. In the simulation example of FIGS. 5 and6, proton density is relatively low at the detection region. In certainproton therapy situations, however, proton beam intensity can besufficiently high, such that even one spill of incident protons canprovide enough collision events to allow effective characterization ofthe interactions. Examples of such high beam intensity situations aredescribed herein in greater detail.

FIGS. 7-9 show measurements of charged particles by the detector 558 ofFIG. 4 when the target volume 554 is subjected to different protonbeams. For the purpose of description of FIGS. 7-9, the beam travelsalong the X direction (positive to negative) and generally centered atsome Y and Z values.

In FIG. 7, a scatter plot 600 shows an interaction profile (in an XYplane) reconstructed by detected charged particles resulting from apencil beam of protons having kinetic energy of about 100 MeV. Theexample pencil beam has an average width of approximately 1 cm and anintensity of approximately 10⁸ protons/spill.

To obtain the scatter plot 600, a track is considered to be valid anddue to a charged particle by requiring coincidence of two Si detectorsets (each with two perpendicular Si strip orientations) and a CesiumIodide crystal. Signals from the two Si detector sets provide trackcandidates, some of which can be validated by requiring deposition ofenergy (greater than approximately 5 MeV) in the CsI crystal. Tracksegments validated in the foregoing manner (and representing chargedparticles) can be projected to an XY plane at a Z value corresponding tothe average Z value of the beam, thereby yielding the X and Y values foreach of the detected charged particles.

The example 100 MeV beam of FIG. 7 can be representative of atherapeutic proton beam. To obtain data similar to that of the examplescatter plot 600, one spill of such a therapeutic proton beam can beused. In the particular example detection configuration yielding thescatter plot 600 of FIG. 7, the detector used had a sensitive area ofabout 6.4 cm×6.4 cm and a restricted data-taking rate. Because of thedetector's restricted data rate, the plot 600 represents datacorresponding to few spills. It is estimated that a detector havingsimilar sized sensitive area can allow generation of sufficient data formeaningful analysis with about one spill (of therapeutic proton beamhaving, for example, about 10⁸ protons per spill) with a higherdata-taking rate and/or detector efficiency of about 90% or higher.

As further shown in FIG. 7, example one-dimensional distributions can beobtained at different locations along the beam direction. A distribution604 is representative of a Y-distribution of charged particles' at theXY plane at an X-slice representative of an entrance portion of the headphantom. A distribution 602 is representative of a Y-distribution ofcharged particles' at the XY plane at an X-slice representative of adepth of about 8 cm into the head phantom.

As shown, a Gaussian fit of the distribution 604 at the entrance yieldsa sigma of about 1 cm at the entrance of the phantom head, and at 8 cmdepth, the profile widens to about 2.2 cm (sigma in the fit of thedistribution 604). It is also noted that the mean Y values obtained fromthe fits are about 2.2 cm at the entrance and about 2.1 cm at the depthof 8 cm. Such peak location values can provide information about theoverall direction of the beam as it traverses and interacts with thetarget volume.

In FIG. 8, a scatter plot 610 shows an interaction profile similar tothat of FIG. 7, but with a pencil beam of protons having kinetic energyof about 250 MeV. The example pencil beam has an average width ofapproximately 0.8 cm and an intensity of approximately 10⁸protons/spill.

To obtain the scatter plot 610, track validation and projection to theXY plane are achieved in manners similar to those described above inreference to FIG. 7. Such a beam can be representative of, for example,a proton beam used for radiosurgery applications. Similar to the 100 MeVproton beam example, the particular example detection configurationyielding the scatter plot 610 of FIG. 8 had a restricted data-takingdetector with a sensitive area of about 6.4 cm×6.4 cm; thus, the exampleplot 610 represents data corresponding to few spills. It is estimatedthat a detector having similar sized sensitive area can allow generationof sufficient data for meaningful analysis with about one spill (ofradiosurgery proton beam having, for example, about 10⁸ protons perspill) with a higher data-taking rate and/or detector efficiency ofabout 90% or higher.

As further shown in FIG. 8, an example Y-distribution 614 isrepresentative of an entrance portion of the head phantom; and anexample Y-distribution 612 is representative of a depth at about 10 cminto the head phantom. As shown, the distribution 614 at the entranceyields a sigma of about 0.6 cm at the entrance of the phantom head, andat 10 cm depth, the profile widens to about 0.75 cm. It is also notedthat the mean Y values obtained from the fits are about 2.3 cm at theentrance and about 2.1 cm at the depth of 10 cm.

In FIG. 9, a scatter plot 620 shows an interaction profile similar tothat of FIG. 8, but with a collimated beam (about 3.5 mm wide) ofprotons having kinetic energy of about 250 MeV. The example beam iscollimated from a beam having an average intensity of approximately 10⁸protons/spill, and the collimation is estimated to pass through about30% of such protons to the head phantom.

To obtain the scatter plot 620, track validation and projection to theXY plane are achieved in manners similar to those described above inreference to FIG. 8. The example detector configuration, its restricteddata-taking rate, and the detection configuration's capability forone-spill sampling are also similar to those described above inreference to FIG. 8.

As further shown in FIG. 9, an example Y-distribution 624 isrepresentative of an entrance portion of the head phantom; and anexample Y-distribution 622 is representative of a depth at about 10 cminto the head phantom. As shown, the distribution 624 at the entranceyields a sigma of about 0.18 cm at the entrance of the phantom head, andat 10 cm depth, the profile widens to about 0.22 cm. It is also notedthat mean Y values can be obtained from the fits.

As described above in reference to FIGS. 4-9, detection of chargedparticles can provide useful information, including information aboutbeam direction and widening of the beam as it traversed the interactionregion. FIGS. 10-12 show similar simulation and measurements where thetarget volume is absent. As is generally known, data obtained in such amanner (sometimes referred to as “target-out” data) can provide usefulinformation about background and systematic effects to be removed fromthe “target-in” data. In certain situations, however, measurements oftarget-out data can provide information about the beam itself.

FIG. 10 shows an example configuration 550 a that is substantially thesame as that of FIG. 4, but with the target volume 554 removed from thebeam 552. Thus, after the protons leave a beam pipe or nozzle through awindow, they interact with, for example, air. It should be noted thatsuch beam-air interactions also exist between the exit window and thetarget volume when the target volume is in place.

FIG. 11 graphically displays tracks representative of secondaryparticles (including photons) resulting from 1,000 interaction events of100 MeV protons with the air. As shown, numerous charged particles aregenerated in the beam-air interactions, with the particles being mostlylow energy electrons and having relatively short mean pathlengths. Thereare, however, a significant number of charged particles that areaccepted by the detector.

In FIG. 12, a scatter plot 630 shows a beam-air interaction profile thatcan be obtained in a manner similar to those of FIGS. 7-9. The exampledetector configuration, its restricted data-taking rate, and sampling offew spills are also similar to those described above in reference toFIGS. 7-9.

As further shown in FIG. 12, an example Y-distribution 632 isrepresentative of a slice of the scatter plot 630 along the beam-airinteraction region. The distribution 632 yields a sigma of about 0.6 cm.A number of such distributions can be obtained at different values of X;and from characterization of such distributions, one or more propertiesof the beam can be obtained. For example, beam divergence in the air andbeam direction can be measured and used for purposes such as treatmentplanning.

FIGS. 4-12 generally show how detection of charged particles can beuseful for characterizing various proton beam interactions with a targetvolume. FIG. 13 shows that in certain embodiments, such charged particledetection features can be implemented in a proton beam based system 640.In certain embodiments, the system 640 can be a proton therapy system,an imaging system, or some combination thereof.

The system 640 can include one or more devices (not shown) configured todeliver a beam of protons 642 to a target volume 644. The target volume644 can be held in place by a support mechanism (not shown in FIG. 13)in known manners.

In FIG. 13, an upstream beam detector 650 can be positioned andconfigured to allow characterization of the beam 642 prior to entry intothe target volume 644. In certain embodiments, a downstream detector(not shown) can also be provided to characterize surviving beam and/ordownstream-directed products resulting from the beam-targetinteractions. Configurations and implementations of one or more of suchbeam related detectors can be based on known devices and techniques; andthus, further description is not needed for FIG. 13.

FIG. 13 further shows that the system 640 can include one or moredetector assemblies 660. In the example shown, two detector assemblies660 a and 660 b are provided, with the first detector 660 a positionedat an angle of θ₁ relative to a beam axis 646, and the second detector660 b positioned at an angle of θ₂.

It will be understood that the first and second detectors 660 a and 660b may or may not be configured the same. Further, the two exampledetector angles θ₁ and θ₂ may or may not be the same. For example,providing a second detector (660 b) may be for the purpose of increasingthe number of accepted charged particles from a given kinematic region.In such a situation, and assuming that there is no magnetic field todistinguish charge signs, a second detector substantially identical tothe first detector can double the number of accepted particles.

In certain situations, however, it may be desirable to have the twodetectors measure different kinematics and/or types of chargedparticles. In such a situation, the first and second detectors 660 a and660 b, and/or the detector angles θ₁ and θ₂, may be configureddifferently.

FIG. 13 further shows that in certain embodiments, a given detectorassembly (e.g., 660 b) can be positioned such that its angle (θ₂) iswithin a selected range (e.g., between angles α₁ and α₂). Non-limitingexamples of how the foregoing detector angles (θ) and angle ranges (Δα)can be selected are described herein in greater detail.

FIG. 13 further shows that the system 640 can include a data acquisitionsystem 670 in communication with the various detectors (e.g., beamdetector 650 and detector assemblies 660 a and 660 b). Configurationsand implementations of such data acquisition system can be based onknown devices and techniques; and thus, further description is notneeded for FIG. 13.

FIG. 13 further shows that the system 640 can include a data analysiscomponent 672 in communication with the data acquisition system 672. Incertain embodiments, the analysis component 672 can receive data fromthe data acquisition system 672 and generate processed data such asinteraction profiles and other quantities described herein.

FIG. 13 further shows that the system 640 can include a displaycomponent 674 in communication with the analysis component 672. Incertain embodiments, the display component 674 can be configured tofacilitate planning of proton therapy based on one or more features asdescribed herein.

FIGS. 14-19 show examples of how one or more detection angles such asangles θ₁ and θ₂ (FIG. 13) can be estimated. In certain embodiments,such estimation can include computer simulation such as that provided byGEANT4 software. FIGS. 14 and 15 depict a target volume 700 defined inGEANT4. Such definition can be user-defined, and in this particularexample, can represent a human head having an outer shell 702approximating a cranial shell and an inner structure 704 approximating abrain material.

In the simulation, a beam of protons 710 can be provided to the targetvolume 700 as follows. A proton beam 710 that is substantiallyinfinitely thin and having substantially monoenergetic protons can beinitiated in a vacuum environment simulating a beam pipe. The beam 710can be configured to exit the beam pipe through an approximately 25 μmthick titanium window at about 2 m upstream of the center of the headphantom 700. The beam 710 can be positioned to enter the head phantom700 substantially laterally.

To obtain information about angles of particles being emitted from thehead phantom 700, a cylindrical shell 712 shaped sensitive volume (ofair) with a radius of approximately 20 cm and a height of approximately18 cm can be positioned about the phantom 700, such that the centers ofthe phantom 700 and the sensitive volume 712 are substantially the same.The example height and radius of the sensitive volume 712 approximatelyrepresents a distance and acceptance of a detector that can bepositioned relative to a head. For example, detector assemblies 714 and716 are depicted as being positioned at the radius of the sensitivevolume 712. It will be understood that such dimensions can varydepending on various therapy and/or imaging systems.

In the simulation, positions and energies of primary protons identifiedto have undergone a nuclear collision within the phantom 700, andsecondary protons, can be recorded by the sensitive shell 712. Thesimulation was repeated for two incident proton energies, approximatelyat 100 MeV representative of Bragg peak based treatments andapproximately 250 MeV representative of radiosurgery applications.

In FIG. 15 (a screenshot of GEANT4 simulation), 20 primary protonshaving 100 MeV kinetic energy and resulting interactions are depicted.Both the air sensitive ring 712 and the detectors (714, 716) are shownfor illustration; however, only the ring is needed in the simulation torecord the capture of various particles from the phantom. Once one ormore preferred detection angles are determined, one or more detectorscan be positioned accordingly so as to facilitate reconstruction ofcharged particles' vertices. In FIG. 15, various short-path lines aboutthe beam 710 represent electrons, and the lengthier lines also emergingfrom the beam 710 and close to the phantom 700 represent gammas.

Based on the foregoing simulation setup, simulated angular distributionsof scattered protons (primary and secondary) are depicted in FIGS. 16and 17. In FIG. 16, an angular distribution 720 results frominteractions of the 100 MeV proton beam with the phantom. In FIG. 17, anangular distribution 730 results from interactions of the 250 MeV protonbeam with the phantom. In both configurations, the beam is incident onthe phantom at about 270 degrees, and the angles indicated in thedistributions (720 and 730) represent emission angles of the protons inthe same coordinate system.

In the 100 MeV case, it is noted that a large portion of the scatteredprotons are backscattered at approximately 270 degrees (peak 726). Lessintense secondary peaks (722, 724) at about 55 degrees and 125 degreesare also present. Relative to the beam axis (90 degrees in FIGS. 16 and17), emission at 270 degrees represent θ (FIG. 13) of 180 degrees, andemissions at 55 degrees and 125 degrees represent θs of +/−35 degrees.

It is also noted that in FIG. 16, a minimum intensity is present atabout 90 degrees. This result is generally consistent with the 100 MeVprotons being stopped substantially within the phantom due to the Braggpeak effect.

In the 250 MeV case, the angular distribution 730 yields a single peak(732) at about 90 degrees, indicating that most of the scattered andsecondary protons are generally directed along the beam direction. Thus,placement of a detector downstream of the target volume and at or nearthe beam axis is likely not be desirable, especially in situations(e.g., radiosurgery) where a high intensity beam of protons generallypunch through the target volume. At such high intensities, the detectorcan be saturated and/or damaged from high radiation doses. Similarly, insituations involving high intensity proton beams (whether or not thebeam stops in the target volume), it is also not likely desirable tohave a detector upstream of the target volume at or near the beam axis,since it will be directly subjected to the high intensity beam.

In certain embodiments, appropriate intensity values acceptable for thedetector can be estimated using angular distributions such as those ofthe foregoing examples. It is estimated that when a beam intensity isabout 10⁸ protons per spill, positioning a pair of detectors at about+/−45 degrees relative to the beam axis (45 degrees and 135 degrees inFIGS. 16 and 17) can result in acceptance of particles attributable tointeractions on the order of 10⁴ protons (per spill) for the 100 MeVcase. For the 250 MeV case, it is estimated that the same positioningcan result in acceptance of particles attributable to interactions onthe order of 10⁵ protons (per spill).

It is noted that for the example 100 MeV case, the less intensesecondary peaks at θs of about +/−35 degrees are about 10 degreesdifferent from the +/−45 degrees referenced in the foregoing estimation.For a detector having a sensitive area of, for example, about 36 cm×18cm, a 10-degree difference does not affect the particle yield greatly.However, it may be desirable to provide such additional 10 degrees fordesign reasons. For example, in proton systems where both proton therapyand proton computed tomography (pCT) are implemented, it may bepreferable to have a detector used for both therapy and pCT. To achievesuch interchangeability, the detector can be positioned downstream ofthe beam (θ≈0 degree) and the system can be operated with a lowerintensity beam suitable for imaging. For therapeutic use, the detector(mounted on, for example, a stiff U-arm) can be rotated to θ of about 45degrees from the beam axis for beam monitoring, and the system can beoperated with a higher intensity beam suitable for therapy.

Based on the foregoing detector positioning and expected acceptance rateestimates, charged particle detectors placed at about +/−45 degrees(relative to the beam axis) yield measured interaction profiles 740 and750 depicted in FIGS. 18 and 19 when the phantom is subjected to about10⁸ primary protons. The example profile 740 represents the 100 MeV beamcase; and the example profile 750 represents the 250 MeV case. In bothcases, the detected charged particle tracks (producing hits in each ofthe consecutive Si strip detector planes) were projected back to animage space. The example image space can be set as an approximately20×20×5 cm³ volume divided into 128×128×25 voxels. The reconstructionwas carried out by registering substantially all voxel-rayintersections. In FIGS. 18 and 19, central slices of the image space areshown.

The images in FIGS. 18 and 19 show nuclear scattering probabilitydistributions 740 and 750 (combined elastic and inelastic), and therebygenerally define where the primary proton beam travels in the targetvolume. Note that the X limits of the elliptical shaped head phantom areat about ±10 cm and the Y limits at about ±7 cm. The beam enters theimage space from about (0,−10).

As shown in FIG. 18, the reconstructed 100 MeV beam shows the largestnumber of scattered protons originating from the approximately 0.8 cmthick skull region as the beam enters the phantom. This is to beexpected due to the higher effective atomic number of the skull material(relative to that of the brain material). Further, the beamsubstantially stops at approximately the center of the phantom (0,0).

As shown in FIG. 19, the reconstructed 250 MeV beam shows the largestscattering density in the skull region as the beam exits the phantom. Inthis example, the vertex of the beam substantially throughout thephantom traversal can clearly be seen. It is noted that the diagonalblurring of the image in FIG. 19 (and also in FIG. 18) is due to thepositioning of the detectors at the above-mentioned angles.

The example images of FIGS. 18 and 19 are generated from about 10⁸primary protons, a number typical for a single treatment beam spill atthe Loma Linda University Medical Center.

In certain embodiments, various features of the present disclosure canfacilitate planning and/or monitoring of proton therapy. In situationswhere such proton therapy system can also be used for imaging purposes(e.g., proton CT), one or more of the features described herein can beimplemented in a detector for detecting and characterizing passage ofimaging protons through the tissue. Further, when the system is switchedfrom imaging mode to therapy mode, the detector can be moved out of thebeam direction and be positioned at one or more of the angles asdescribed herein so as to provide the planning and/or monitoringfunctionalities while avoiding high intensity beams typically associatedwith therapy.

In certain embodiments, the detector can be positioned so as to acceptcharged particles emitted from an approximate center of the targetregion at an angle (relative to the beam direction) in a range ofapproximately 20 to 90 degrees. In certain embodiments, the angle is ina range of approximately 25 to 70. In certain embodiments, the angle isin a range of approximately 30 to 60. In certain embodiments, the angleis in a range of approximately 35 to 55. In certain embodiments, theangle is in a range of approximately 40 to 50. In certain embodiments,the angle is approximately 45 degrees.

In the context of proton beam therapy, the foregoing estimation of therelative stopping power distributions of protons in a given phantom canfacilitate accurate estimation of deposited dose to the phantom.Further, a pre-treatment estimation of the proton's relative stoppingpower distribution based on, for example, one initial spill of thetherapeutic beam, can be facilitated by charged particle detectormodules positioned and operated as described herein.

As described herein, one or more features of the present disclosure canbe implemented in a proton therapy system and/or a proton-based imagingsystem such as a proton-CT system. FIGS. 20A and 20B show that incertain embodiments, one or more features of the present disclosure canbe implemented in systems such as that found at the Loma LindaUniversity Medical Center.

In FIGS. 20A and 20B, first and second orientations of one embodiment ofa particle radiation therapy system are schematically illustrated. Otherembodiments of proton therapy systems are described in U.S. Pat. No.4,870,287 of Sep. 26, 1989, which is incorporated herein in its entiretyby reference. The radiation therapy system is designed to delivertherapeutic radiation doses to a target region within a patient 08 fortreatment of malignancies or other conditions from one or more angles ororientations with respect to the patient 08. The system includes agantry 02 which includes a generally hemispherical or frustoconicalsupport frame for attachment and support of other components of theradiation therapy system. Additional details on the structure andoperation of embodiments of gantries may be found in U.S. Pat. No.4,917,344 and U.S. Pat. No. 5,039,057, both of which are incorporatedherein in their entirety by reference.

The system also comprises a nozzle 04 which is attached to and supportedby the gantry 02 such that the gantry 02 and nozzle 04 may revolverelatively precisely about a gantry isocenter 20. The system alsocomprises a radiation source 06 delivering a radiation beam along aradiation beam axis 40, such as a beam of accelerated protons. Theradiation beam passes through and is shaped by an aperture 10 to definea therapeutic beam delivered along a delivery axis 42. The aperture 10is positioned on the distal end of the nozzle 04 and the aperture 10 maypreferably be specifically configured for a patient's particularprescription of therapeutic radiation therapy. In certain applications,multiple apertures 10 are provided for different treatment fractions.

In the embodiment of FIGS. 20A and 20B, the system also comprises one ormore sensors 12 a, 12 b. In some embodiments, the sensors 12 a, 12 b canbe retractable with respect to the gantry 02 between an extendedposition and a retracted position. The sensor(s) 12 can comprise“imaging” sensors adapted to detect a location through which a protonand/or x-ray photon passes. The sensor(s) 12 can also, in addition or asan alternative, comprise a calorimeter capability to determine an impactenergy of an incident proton. Where provided, a retractable feature ofthe sensor(s) 12 provides the advantage of withdrawing the sensor(s) 12from a delivery axis 42 of a radiation source 06 when the sensor(s) 12is not needed thereby providing additional clearance within the gantry02 enclosure. In certain embodiments, one or more of the sensors 12,and/or one or more separate sensors, can be positioned and operatedaccording to the present disclosure so as to provide one or morefunctionalities as described herein.

The system can also comprise one or more x-ray sources 30 whichselectively emit appropriate x-ray radiation along one or more x-raysource axes 44 so as to pass through interposed patient tissue togenerate a radiographic image of the interposed materials via thesensor(s) 12. The particular energy, dose, duration, and other exposureparameters preferably employed by the x-ray source(s) 30 for imaging andthe radiation source 06 for therapy/analysis will vary in differentapplications.

The system may also comprise a patient positioner 14 and a patient pod16 which is attached to a distal or working end of the patientpositioner 14. The illustrative patient positioner 14 is adapted to,upon receipt of appropriate movement commands, position the patient pod16 in multiple translational and rotational axes and preferably iscapable of positioning the patient pod 16 in three orthogonaltranslational axes as well as three orthogonal rotational axes so as toprovide a full six degree freedom of motion to placement of the patientpod 16.

The patient pod 16 is configured to hold the patient 08 securely inplace in the patient pod 16 so to as substantially inhibit any relativemovement of the patient 08 with respect to the patient pod 16. Invarious embodiments, the patient pod 16 comprises expandable foam, biteblocks, and/or fitted facemasks as immobilizing devices and/ormaterials. The patient pod 16 may also be configured to reducedifficulties encountered when a treatment fraction indicates delivery atan edge or transition region of the patient pod 16.

FIG. 20B shows the same system as FIG. 20A, but with gantry rotationabout an angle 0 with respect to the configuration shown in FIG. 20A.The radiation beam axis 40 is still arranged to pass through the gantryisocenter 20. FIGS. 20A and 20B also illustrate an embodiment whereinthe sensors 12 a, 12 b are not opposed symmetrically about the gantryisocenter 20. Rather, in this embodiment, the sensors 12 a, 12 b arearranged substantially perpendicular or at a 90° orientation withrespect to each other. It will also be understand that while FIGS. 20Aand 20B illustrate arrangements of two sensors 12 a, 12 b, this is not arequirement and other numbers and arrangements of sensors 12 arepossible.

FIG. 21 schematically illustrates embodiments of a proton analysissystem 100 referred to hereafter as system 100 for brevity. The system100 is configured to detect and analyze one or more characteristics ofaccelerated protons provided by an accelerated proton therapy system,for example as previously described and illustrated with respect toFIGS. 20A and 20B. The system 100 can be further configured todetermine, based at least in part on the one or more measuredcharacteristics of the accelerated protons, various characteristics ofmaterials in the path of the accelerated protons, a path of individualor groups of protons and/or characteristics of patient tissue throughwhich the accelerated protons have passed. In certain embodiments, suchcharacterization of the proton beam and/or the tissue can be achieved byconfiguring and operating the system (e.g., detecting scattered protons,charged particles and/or secondary particles) as described herein.

For example, embodiments of the system 100 are capable of determining animpact energy of an accelerated proton. By knowing an initial energy ofthe proton as provided by a proton therapy system, the system 100 candetermine an energy loss experienced by the proton in traversing thematerial of interest. This information can be utilized to calculate anestimate of relative electron density and/or atomic numbers of nucleiwithin a target region.

In some embodiments, the system 100 is capable of estimating a spatialposition of impact of an accelerated proton, a secondary proton, and/orother secondary particles. Although mainly in the context of accelerated(primary) protons, some or all of the features described in reference toFIGS. 20-27 can also be applied to secondary protons and other chargedparticles. In at least some instances, the accelerated proton will havebeen deflected from an initial path and a determination of the amount orangle of scattering can be utilized to provide indications of therelative atomic number of the material having had deflected the proton.

In some embodiments, determination of relative spatial position ofimpact of a deflected proton can be used as a data point in calculationof a point of origination of the accelerated proton. With a plurality ofsuch data points provided by a plurality of accelerated proton impacts,the system 100 can computationally reconstruct an original spatial pathof the protons thereby providing a direct measurement and confirmationof an actual path of a proton therapy beam that may be deviated from anintended or nominal path.

Such determinations are useful, for example in a treatment planningstage for more accurately implementing a treatment plan by providingempirical measurements of beam path and interaction of the beam withtarget tissue. For example, some embodiments can more accuratelydistinguish tissue boundaries and/or provide measurement data indicatinga dose delivered to a given target/region. Embodiments can also providein-process feedback to facilitate more accurate delivery of the plannedtreatment and determine any indicated adjustments, for example beamdirection, initial energy, dose, and the like. In some embodiments,determination and implementation of any indicated adjustments can beperformed automatically. In some embodiments, determination andimplementation of any indicated adjustments can be performed during atreatment session. These and other advantages and features ofembodiments will be more clearly understood with the following detaileddescription and illustration of features of the system 100.

In some embodiments, the system 100 comprises one or more first sensors102. In one exemplary non-limiting embodiment, the system 100 comprisesa pair of opposed first sensors 102, including sensors 102 a, 102 b and102 c, 102 d. In some embodiments, the first sensors 102 comprisesubstantially planar silicon strip detectors configured to generate asignal upon impact of an accelerated proton. In other embodiments, thesensors 102 may include any other suitable type of proton detector. Insome embodiments, each individual of a pair of associated first sensors102 are each arranged to be substantially coplanar with the other of thepair of first sensors 102 and to be separated by a distance d from eachother. For example, sensors 102 a and 102 b of FIG. 21 are coplanar andseparated by the distance d, and sensors 102 c and 102 b are coplanarand separated by the distance d. In other embodiments, respective pairsof sensors 102 may be separated by different distances. By providing apair of substantially coplanar first sensors 102 separated from eachother, the system 100 is capable of obtaining two independent butassociated data points generated by impact of a given acceleratedproton. By obtaining two independent measurements of spatial impactpoints of a given accelerated proton, the system 100 can employ any of avariety of algorithms to mathematically extrapolate a statisticallylikely path of a given proton.

In some embodiments, the system 100 comprises one or more second sensors104. The second sensors 104 (where provided) may be configured to detectan incident accelerated proton and to determine an impact energythereof. In one embodiment, the second sensors 104 comprisedmulti-crystal proton calorimeters. It will be understood that someembodiments combine both first sensors 102 and second sensors 104, forexample so as to comprise a combined sensor such as the sensors 12 a, 12b of FIGS. 20A, 20B. In embodiments where first sensors 102 are providedin combination with second sensors 104, it will generally be preferredthat the first sensors 102 be arranged upstream of the second sensors104, e.g. such that an incident accelerated protons first impact thefirst sensors 102, pass therethrough, and then impact the second sensors104.

In order to more accurately monitor the characteristics of the incidentaccelerated protons, in at least some embodiments it is preferred thatthe first sensors 102 be capable of tracking an impact location of aproton with a spatial accuracy of better than 100 μm. It is alsopreferred that the second sensors 104 be capable of determining animpact energy and thus an associated energy loss with a resolution ofapproximately one percent or less. In other embodiments, however,spatial accuracy of the first sensors may be less than 100 um and theresolution of the energy loss approximated by the second sensors 104 maybe greater than one percent.

In some embodiments, one or more of the first and second sensors 102,104 are substantially fixed in place. In some embodiments, one or moreof the first and second sensors 102, 104 can be capable of movement. Insome embodiments, one or more first and second sensors 102, 104 arearranged for simultaneous synchronized movement. For example, at leastone pair of first sensors 102 and/or an associated second sensor 104 canbe coupled for movement for example via the gantry 06 with a radiationsource as indicated by the arrow. Thus, the first and/or second sensors102, 104 can be coupled such that any movement of the radiation sourceand the corresponding therapeutic proton beam is matched bycorresponding movement of the first and/or second sensors 102, 104.These embodiments provide a consistent spatial relative orientationbetween the first and second sensors 102, 104 and any required movementof the radiation source, for example to provide different treatmentfractions to the patient 08.

The system 100 further comprises data connections 106, including dataconnections 106 a, 106 b, 106 c, 106 d, between the first sensors 102and a data acquisition module 112. The system 100 further comprises dataconnections 110 between the second sensors 104 and the data acquisitionmodule 112. The data connections 106, 110 in some embodiments comprisewired connections. The data connections 106, 110 can in otherembodiments comprise fiber optic cabling. In some embodiments, the dataconnections 105, 110 can comprise wireless communications. Theparticular configuration of the data connections 106, 110 is notessential to practicing the described embodiments and the particularimplementation can be selected based on the requirements of theparticular application.

However, it will generally be preferred that the data connections 106,110 as well as the associated first and second sensors 102, 104 becapable of relatively high data rates. In some implementations, it ispreferred that these components be capable of accommodating data ratesof one megabit per second or greater. It will also be generallypreferred that these components be hardened against exposure toradiation, such as the accelerated protons and x-ray radiation that isat least intermittently present in a radiation therapy environment. Itwill also generally be preferred that the components be resistant orhave an ability to properly function in an environment having arelatively strong and variable magnetic field, as is also at leastintermittently present in a proton radiation therapy setting.

The data acquisition module 112 is configured to receive data signalsfrom the first and second sensors 102, 104 via the respective dataconnections 106, 110. The data acquisition module 112 can comprise andprovide appropriate buffering, amplification, level shifting,multiplexing, synchronization, and similar functions as required forappropriate acquisition and utilization of the data signals provided bythe sensors 102, 104.

The system 100 can further comprise a computing device 114 including oneor more processors that interfaces with various other components of thesystem 100 and generates user interfaces for display by an operator, forexample. In the embodiment of FIG. 21, the computing device communicateswith the data acquisition module 112 and obtains appropriate data orsignals corresponding to the measurements obtained by the first andsecond sensors 102, 104. The computing device 114 can compriseappropriate algorithms, software, firmware, and/or hardware to operateon the data obtained from the data acquisition module 112 and a displayto provide indications to a clinician or other user of the observedcharacteristics of accelerated protons as obtained and provided by thesystem 100. Additional details of the data manipulation and outputprovided by the system 100 will be provided below following a furtherexplanation of components and functions of the system 100.

FIG. 22 illustrates an additional embodiment on a configuration ofsystem 100. The embodiment of system 100 illustrated in FIG. 22 isgenerally similar to the embodiments of system 100 illustrated in FIG.21 and includes components, such as the data connections 106, 110 anddata acquisition module 112, however which are not illustrated in FIG.22. The embodiments illustrated in FIG. 22 differ by comprising anopposed pair of first sensors 102 a, 102 b arranged opposite from a pairof first sensors 102 c, 102 d. The embodiments illustrated in FIG. 22further comprise a pair of opposed second sensors 104 a, 104 b. In thisembodiments, the opposed pair of first sensors 102 a, 102 b and 102 c,102 d and the opposed second sensors 104 a, 104 b are arranged oppositeand substantially symmetrically on opposite sides of a proton beam 120.The proton beam 120 is directed to pass between the sensors 102 b and102 c, but is not arranged to directly impact the sensors. The protonbeam 120 is further arranged to align with and pass through a targetisocenter 122 in a target region 124. The target region 124 can comprisea wide variety of materials, including inanimate and living tissue. Oneor more of the opposed pair of first sensors 102 a, 102 b and 102 c, 102d and the opposed second sensors 104 a, 104 b can be configured formovement as indicated by the arrow. In some embodiments, the opposedpair of first sensors 102 a, 102 b and 102 c, 102 d and the opposedsecond sensors 104 a, 104 b move substantially in synchrony with eachother, for example as coupled to movement of the gantry 02.

As illustrated in FIGS. 20A, 20B, 21, and 22, a radiation sourceproviding the proton beam 120 can be moved, for example rotated, withrespect to one or more of the sensors 102, 104. Thus, FIG. 22 forexample illustrates that the proton beam 120 can pass between opposedsensors 102, 104 which are arranged substantially symmetrically aboutthe proton beam 120. FIG. 21 in contrast illustrates that a proton beam120 can be arranged to directly target and pass through first sensors102 a, 102 b, 102 c, 102 d and then impact into a second sensor 104. Itwill be further understood that a wide variety of orientations andrelative positions between the proton beam 120 and the system 100 can bearranged and that the substantially orthogonal (perpendicular orparallel) orientations illustrated in FIGS. 21 and 22 are simply someexamples of possible measurement orientations that can be supported bythe system 100.

FIGS. 23A and 23B illustrate configurations embodiments of the system100 comprising first and second sensors 102, 104 arranged on only asingle side of a target region 124 (FIG. 23A) and on opposed sides ofthe target region 124 (FIG. 23B). A proton source 126 provides theproton beam 120 in a relatively tightly focused or pencil beam tointersect the target region 124. FIGS. 23A and 23B illustrate atransverse view or a view generally perpendicular to the proton beam120. FIGS. 23A and 23B further illustrate views along a directionsubstantially parallel to the first and second sensors 102, 104. As willbe understood, a wide variety of energies and doses of the proton beam120 can be provided depending on the needs of a particular application.With selection of a high enough energy of the protons, the proton beam120 can be configured to substantially pass through the target region124. Selection of a more moderate energy of the proton beam 120 canresult in a measurable proportion of the proton beam 120 deflecting fromthe target region 124 and impacting the sensors 102, 104. Suchinteractions can yield a number of charged particles (indicated as 130).In certain embodiments where magnetic field is applied to differentiatepositive and negative charged particles, providing two detectors (FIG.23B) can facilitate separation and identification of differently chargedparticles emerging from the target region 124. By analyzing thecharacteristics of the deflected protons and/or other charged particles,for example the relative spatial position of the deflected protons 130and/or their remaining energy, the system 100 can provide valuableindications of the characteristics of the target region 124 and theproton beam 120.

FIG. 24 illustrates schematically in side section view a furtherconfiguration of the system 100. As can be seen, the proton beam 120follows an initial path and is arranged to intersect a first pair offirst sensors 102 a, 102 b substantially perpendicular to a major planeof the first sensors 102 a, 102 b. The first sensors 102 a and 102 b arearranged to be substantially parallel with each other and to have aspacing d₁ therebetween as previously described. The first sensors 102 cand 102 d are arranged to be substantially parallel with each other andto have a spacing d₂. The distances d₁ and d₂ can be substantially thesame or can differ. The proton beam 120 substantially passes through thefirst sensors 102 a, 102 b and impacts a second pair of first sensors102 c, 102 d. However, for at least certain mean proton energies, thedeflected protons 130 define at a least a degree of divergence ofindividual protons from the initial path of the proton beam 120.

FIG. 25 is a graph illustrating an exemplary divergence of the deflectedprotons due to, for example, multiple Coulomb scattering. As illustratedin FIG. 25, the individual protons of the proton beam 120 have aninitial energy indicated E₀. While the proton beam 120 in at leastcertain implementations preferably comprises a relatively tightlyfocused beam, the proton beam 120 will in practice have a non-zero widthas schematically indicated by the vertical spacing of the individualrays of the proton beam 120. The individual protons of the proton beam120 impact the target region 124 at a first object boundary indicated asu₀ and leave the target region 124 at a second object boundary indicatedu₂. A path of an individual proton is illustrated schematically todescribe a plurality of deflections within the target region 124. Thesum result of these individual plurality of deflections can result in agiven proton diverging from an initial or nominal path indicated by thehorizontal straight line and indicated with the designator 132. Thisdeflection from the initial or nominal path 132 can comprise one or bothof an off-axis translation indicated by the designator 134 by a distanceindicated t₂ and/or by a deflection angle 136 indicated also by theangle Θ₂.

Information about the path and energy of a given proton can be obtainedand considered based on observations regarding the proton as the protonpasses through a first sensor pair of sensors (e.g., 102 a, 102 b ),where the pair of sensors comprise an entry registration plane 140, forexample. The entry registration data provides initial informationregarding the proton, for example including an initial or nominal pathvector 132 and an initial energy E₀. An exit registration plane 142, forexample comprising a second pair of sensors (e.g., 102 c, 102 d ),provides corresponding exit registration data including any deflectionangle 136 and off axis translation 134 and exit energy indicated E₂.

Energy loss experienced by a proton traversing the target region 124corresponds to relative electron density η_(e) along the path followedby the proton. Thus, an energy loss integral between the exit energy E₂and the initial energy E₀ corresponds to a path integral of electrondensity within the target region 124 along that path. By analyzing aplurality of such energy losses by individual protons, the system 100provides a clinician valuable information about the internalcharacteristics of the target region 124 without directly physicallyaccessing the target region 124. The energy loss can be represented bythe following equations.

$\frac{dE}{du} = {{F(E)}{\eta_{e}(u)}}$${\int_{E_{2}}^{E_{0}}{\frac{1}{F(E)}\ {E}}} = {\int_{L}^{\;}{{\eta_{e}(u)}\ {u}}}$

In a similar manner, the variance of the scattering angle of thedeflected protons 130 is indicative of a relative atomic number ξ_(z) ofthe target region 124. The relationship between scattering angle andatomic number can be represented by the following equations.

$\frac{d\; \sigma_{\theta}^{2}}{du} = {{G\left( {{p(u)},{\beta (u)}} \right)}{\xi_{Z}(u)}}$∫₀^(θ₂²) σ_(θ)² = ∫_(L) G(p(u)ξ_(Z)(u)) u

As previously described and illustrated with respect to FIG. 23,deflected protons 130 from a proton beam 120 that is not directed tointercept first and second sensors 102, 104 can nonetheless be at leastpartially detected by the first and/or second sensors 102, 104. Whileprotons have a non-straight statistical path, information about thespatial location of impacts of the deflected protons 130 can be analyzedto determine a spatial location of the initial path of the proton beam120.

Each individual proton detected can provide independent informationabout itself and a target region 124. As the history of a given protonis inherently discreet, some embodiments employ discreet approaches inanalyzing and utilizing data obtained from the protons. The targetregion 124 can be conceptualized as a black box object comprising athree dimensional spatial distribution of target parameters x that canproduce corresponding measured data y. Recovery of the target parametersx under an object function F from the measured data y requires inversionof the operator F.

Fx=y solve=>x=F ⁻¹ y

A discreet linear problem approach requires that the target parameterand measured data both be vectors and the operator F be a matrix.

A variety of discreet approaches in analyzing the measured data, forexample spatial positions through which the protons pass and/or initialand subsequent proton energies, are possible including a filtered backprojection (FBP) as well as algebraic reconstruction techniques (ART).In at least certain implementations, utilization of a most likely path(MLP) in combination with an algebraic reconstruction technique canprovide improved spatial resolution.

As previously noted, a variety of algorithms and approaches can beutilized in analyzing the data measurements obtained by the system 100.Each algorithm or approach can have individual advantages anddisadvantages and the selection of an appropriate algorithm can dependon a variety of factors including but not limited to availableprocessing capability, speed requirements, resolution/accuracyrequirements, and the like.

Exemplary algorithms can include a fully sequential algebraicreconstruction technique (ART) such as Kaczmarz algorithms as used forexample in computed tomography. The fully sequential ART is a standardapproach and has been used in numerous previous applications. Fullysequential ART is known to work in proton computed tomography. However,a fully sequential ART algorithm can be slow due to its sequentialnature. In principal, a fully sequential ART can be modified forparallel operation.

A fully simultaneous approach, (e.g. Cimmino 1937) converges to a leastsquares minimum, however is typically relatively slow due to smallweight factors (1/m). A block iterative projection (BIP) (Aharoni andCensor 1989) provides simultaneous projection within blocks of hyperplanes. The sequential projection of blocks iterates with weightingaccording to block size. This avoids the drawbacks of a small 1/m. Astring averaging algorithm (Censor, Elfving, and Herman 2001) utilizessequential projection within strings of hyper planes and operates inparallel within all strings. A convex combination of all stringsiterates. Component averaging (CAV) (Censor, Gordon, and Gordon 2001) isfully simultaneous similarly to Cimmino's algorithm of 1937. CAVreplaces 1/M weighting factor by a family of diagonal matrices withdiagonal elements equal to number of protons intersecting a jth voxel.CAV leads to nonorthogonal projections and can be made block iterative(BICAV). A diagonally relaxed orthogonal projection (DROP) (Censor,Herman, Elfving, Touraj 2008) is also fully simultaneous like CAV andCimmino's algorithm. DROP employs component average weighting as in CAV,but with orthogonal projection. DROP can also be made block iterative(BIDROP).

As such projection or reconstruction algorithms are highlycomputationally intensive, particularly considering the large amounts ofdata points involved, hardware acceleration of the processing isgenerally advantageous. General purpose graphics processing unitsprovide useful advantages in accelerating the computational processesand are also widely available and relatively inexpensive to purchase anduse.

FIG. 26 illustrates an embodiment of first sensor 102. The first sensor102 comprises a silicon detector plane embodied as a single printedcircuit board. Each first sensor 102 comprises four silicon stripdetectors arranged two on each side. Each silicon strip detector isapproximately nine centimeters by nine centimeters in size. The frontside silicon strip detectors have the strips thereof oriented in a firstdirection, for example a horizontal direction. The correspondingbackside silicon strip detectors have strips oriented in a seconddirection, for example a perpendicular vertical direction. In otherembodiments, the number and sizes of the silicon strip detectors variesand/or other types of detectors may be used.

The strips of the silicon strip detectors comprise relatively narrowdoped strips of silicon forming diodes. As previously noted, it isdesired that the resolution of the first sensors 102 be relatively highand thus the strips of the silicon strip detectors are preferably formedwith widths of approximately 100 μm or less. The diodes of the siliconstrip detectors are reversed biased. As incident accelerated protonspass through the strips, ionization currents occur which are detectedand measured. By monitoring which of the strips extending in the firstdirection and in the second direction are activated in unison, a spatiallocation of the impact of the accelerated proton with the first sensor102 can be determined. This location information is communicated via thedata connection 106 to the data acquisition module 112 for processing bythe processor and user interface 114 as previously described.

FIG. 27 is a flow chart illustrating embodiments of methods of analyzingaccelerated protons, for example in context of a proton therapy system.The embodiments illustrated and described with respect to FIG. 27include a variety of features and a variety of subsets of theillustrated and described features can be employed in variousembodiments.

The method 200 begins in a start block 202. In embodiments where themethod 200 includes therapeutic application of an accelerated protonbeam to treat one or more patient conditions, the start block 202 caninclude an initial diagnosis and treatment plan. For example, the startblock 202 can include a clinician evaluating a patient's particularcondition and prescribing a treatment plan, for example including dosesand energies of a therapeutic proton beam and desired approach vectors.The start block 202 can also include positioning the patient in adesired treatment pose.

In a block 204, a stream of accelerated protons is generated. Thegeneration of accelerated protons in block 204 can include generatingprotons of a known mean initial energy.

In a block 206, the stream of accelerated protons generated in the block204 is directed along a nominal path towards an intended target. In someapplications, the nominal path is selected such that a Bragg peak of theprotons is substantially coincident with a selected region or volumewithin a patient. It will be understood that the nominal path in orderto have a Bragg peak occur at a desired location is dependent on anumber of factors including but not limited to focus of the beam,initial beam energy, and material/tissue through which the beam passes.

As previously noted, predicatively estimating an appropriate nominalpath and initial beam energy to achieve Bragg peak occurrence at adesired position is problematic and subject to numerous inaccuracies anderrors. Embodiments of the method 200 can include the feature ofempirical measurements of the interaction between the proton beam andthe intended target to allow a clinician to adjust one or moreparameters of the proton beam, as indicated, to more accurately achievethe desired interaction between the proton beam and the target.

In a block 210, one or more characteristics of at least some protonsfrom the proton beam are measured. These characteristics can include oneor more of spatial positions through which the protons pass, an incidentenergy of a proton, a translational displacement of a proton from anexpected path, and/or an angle of divergence of a proton from anexpected path. These measurements can proceed according to any of thepreviously described embodiments.

The measurements of block 210 result in data that is indicative of themeasurements performed in block 210. For example, the measurements ofblock 210 can result in data, e.g. a digitized word, indicative of aparticular measurement and/or for a number of different discreetmeasurements. In a block 212, the measurement data is communicated toone or more processors. The one or more processors can be local to aproton therapy system and/or can be remotely located. As previouslynoted, the communication of block 212 can occur in a variety of mannersincluding but not limited to wireless communication, wiredcommunication, fiber optic cables, and the like.

In a block 214, the processors analyze the data and calculate one ormore characteristics of the proton beam and/or target from the empiricaldata obtained in block 210. As previously described, a variety ofcharacteristics of the proton beam and/or the target can be determinedbased on the observed characteristics of individual protons from thebeam. For example, an electron density of tissue/material through whichthe proton beam has passed can be determined based on the observedcharacteristics of the individual protons. The electron density isindicative of the material constitution of the target region and can behelpful, for example, in discriminating diseased tissue from healthytissue.

Similarly, indications of the atomic number of material in the targetregion can be inferred from the measured characteristics observed inblock 210 and can also provide information indicative of the materialconstitution of the target region. Data from a plurality of protonsmeasured in block 210 can be analyzed to regressively reconstruct a mostlikely path of the protons and be utilized to empirically calculate anestimation of an actual beam path. If an empirically determined mostlikely beam path differs from the intended nominal path, a clinician canadjust a proton therapy system to more accurately align an intendednominal path of the proton beam with the desired target. Similarly, ifempirical measurements from block 210 indicate that the Bragg peak isnot occurring with a desired coincidence with the target region, theclinician can adjust one or both of the nominal path and an initialenergy of the proton beam to more accurately align the Bragg peak withthe intended location.

Thus, the method 200 can include a decision block 216 where adetermination is made whether the proton beam needs to be varied oradjusted. If the determination of block 216 is negative, e.g. that theorientation and initial energy/dose of the proton beam is proceedingwithin acceptable parameters, the proton beam can continue to beprovided under the existing conditions for the duration of the indicatedtreatment fraction. However, if the determination of decision block 216is affirmative, a block 220 can be implemented wherein one or moreparameters of the beam is adjusted. In some embodiments, any indicatedadjustments can be performed in real time, e.g. during a treatmentsession. In some embodiments, any indicated adjustments can be preformedautomatically by the system 100. As previously noted, these parameterscan include one or more of an initial energy, a nominal path or spatialvector, and/or a treatment dose. Proceeding from a negativedetermination of block 216 or from block 220, the method 200 wouldgenerally iterate sequentially through blocks 204, 206, 210, 212, 214,and 216 as previously described through the duration of the treatmentsession.

Conditional language, such as, among others terms, “can,” “could,”“might,” or “may,” and “preferably,” unless specifically statedotherwise, or otherwise understood within the context as used, isgenerally intended to convey that certain embodiments include, whileother embodiments do not include, certain features, elements and/orsteps.

Many variations and modifications can be made to the above-describedembodiments, the elements of which are to be understood as being amongother acceptable examples. Thus, the foregoing description is notintended to limit the scope of protection.

What is claimed is:
 1. A proton therapy system comprising: a supportdevice configured to support a volume of tissue and expose at least aportion of the volume of tissue to a beam of protons, the beam ofprotons configured for therapeutic treatment of at least a portion ofthe volume of tissue, the beam of protons defining a beam axis extendingthrough the volume of tissue; a charged particle detector disposedrelative to the volume of tissue and configured so as to detect chargedparticles resulting from interactions of the beam of protons with thevolume of tissue, the charged particle detector having an acceptancerange about a detector axis that extends through a selected location inthe volume of tissue and along the beam axis, the detector axis formingan angle with respect to a forward direction of the beam axis, the anglebeing within a range of approximately 20 degrees to 90 degrees, thecharged particle detector configured to facilitate reconstruction oftracks associated with the detected charged particles, the detectionresulting in generation of signals; and a computing device incommunication with the detector and configured to receive the signalsand generate data having information that allows the reconstruction ofthe tracks so as to allow estimation of locations of the interactions inthe volume of tissue.